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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:p>EPSP\u2013spike (E-S) potentiation is a form of plasticity defined by a persistent increase in neuronal spike output for a given synaptic input, reflecting enhanced E-S coupling independent of synaptic strength. However, its cellular mechanisms remain poorly understood. Here, we show that brief induction of E-S potentiation triggers a sustained calcium activity increase in astrocytes adjacent to the hippocampal CA1 pyramidal layer. Mechanistically, E-S potentiation critically requires GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) localized to the neuronal soma. Sustained astrocytic activity promotes E-S potentiation through vesicular release of D-serine, which enhances tonic activation of somatic NMDARs, suppresses A-type potassium currents, and produces a lasting increase in neuronal excitability. Functionally, this astrocyte-dependent E-S potentiation lowers the threshold for subsequent long-term potentiation, conferring a metaplastic influence on hippocampal circuits. These findings identify an astrocyte-neuron signaling mechanism that drives intrinsic plasticity and establish somatic NMDARs as a key site of astrocytic regulation of hippocampal output.<\/jats:p>","DOI":"10.1073\/pnas.2607168123","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:03:09Z","timestamp":1791831789000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytic facilitation of somatic NMDARs underpins hippocampal E-S potentiation"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1425-1823","authenticated-orcid":false,"given":"Xi","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Minister of Education Frontiers Center for Brain Science, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4058-5280","authenticated-orcid":false,"given":"Zhaohui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Minister of Education Frontiers Center for Brain Science, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7014-8257","authenticated-orcid":false,"given":"Yi","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Minister of Education Frontiers Center for Brain Science, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8793-8623","authenticated-orcid":false,"given":"Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Minister of Education Frontiers Center for Brain Science, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-564X","authenticated-orcid":false,"given":"Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Minister of Education Frontiers Center for Brain Science, Fudan University","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Minister of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1973.sp010273"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1980.sp013256"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10129"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90329-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4217-04.2005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13490"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301512"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","unstructured":"J. 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